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• Azathioprine and cyclosporine for myasthenia gravis in pregnancy
  Alexander F. Lipka
  Published on: 11 February 2015

• Published on: 11 February 2015

  Azathioprine and cyclosporine for myasthenia gravis in pregnancy

  • Alexander F. Lipka, MD
  • Other Contributors:
    • Jan J. Verschuuren

  We read the recently published UK guideline for treating myasthenia gravis (MG) patients in pregnancy with great interest [1]. As stated by the workgroup in their article, few studies are available concerning drug safety in pregnancy in these patients. In our experience, most drugs indeed carry a very small risk in the treatment of MG during pregnancy. However, based on additional literature we would advise some caution...

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  We read the recently published UK guideline for treating myasthenia gravis (MG) patients in pregnancy with great interest [1]. As stated by the workgroup in their article, few studies are available concerning drug safety in pregnancy in these patients. In our experience, most drugs indeed carry a very small risk in the treatment of MG during pregnancy. However, based on additional literature we would advise some caution regarding use of azathioprine and cyclosporine during pregnancy.

  Cleary and others described pregnancy outcomes in 476 women using AZT during early pregnancy, mostly for inflammatory bowel disease [2]. A significant increase in atrioventricular septum defects was found (OR 3.18), pre-term birth, low birth weight and small stature were also more significant. A trend towards an increase in all birth defects was found (OR 1.41, 95% CI 0.98-2.04) was found in women with IBD and azathioprine, compared to IBD patients without azathioprine.

  For cyclosporine, a meta-analysis of multiple studies shows a non- significant increase of malformations (OR 3.83, 95% CI 0.75-19.6) and borderline significant prematurity (OR 1.52, 95% CI 1.00-2.32) [3]. Although inconclusive, the limited data available suggests at least some caution. Overall, prematurity and low birth weight are reported more frequently in women exposed to cyclosporine, although it is unclear if these are related to cyclosporine or maternal disease [4].

  In our opinion, both azathioprine and cyclosporine cannot be considered completely safe. Although both are unlikely to be major teratogens, we consider both to be relatively contra-indicated. Our recommendation would be

  1) to discuss the small risks associated with use of azathioprine and cyclosporine and

  2) to discontinue both immunosuppressants from planned conception and during the first trimester in patients with stable disease and no or mild weakness.

  References

  1. Norwood F, Dhanjal M, Hill M, et al. Myasthenia in pregnancy: best practice guidelines from a U.K. multispecialty working group. J Neurol Neurosurg Psychiatry. 2014 May;85(5):538-43.

  2. Cleary BJ, Kallen B. Early pregnancy azathioprine use and pregnancy outcomes. Birth Defects Res A Clin Mol Teratol. 2009 Jul;85(7):647-54.

  3. Bar Oz B, Hackman R, Einarson T, et al. Pregnancy outcome after cyclosporine therapy during pregnancy: a meta-analysis. Transplantation. 2001 Apr 27;71(8):1051-5.

  4. Paziana K, Del Monaco M, Cardonick E, et al. Ciclosporin use during pregnancy. Drug Saf. 2013 May;36(5):279-94.

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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